The Effect of Inhaled Corticosteroid Withdrawal and Baseline Inhaled Treatment on Exacerbations in the IMPACT Study. A Randomized, Double-Blind, Multicenter Clinical Trial.

Abstract

Rationale: In the IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial, fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) significantly reduced exacerbations compared with FF/VI or UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations.Objectives: To understand whether inhaled corticosteroid (ICS) withdrawal affected IMPACT results, given direct transition from prior maintenance medication to study medication at randomization.Methods: Exacerbations and change from baseline in trough FEV1 and St. George's Respiratory Questionnaire results were analyzed by prior ICS use. Exacerbations were also analyzed while excluding data from the first 30 days.Measurements and Main Results: FF/UMEC/VI significantly reduced the annual moderate/severe exacerbation rate compared with UMEC/VI in prior ICS users (29% reduction; P < 0.001), but only a numerical reduction was seen among prior ICS nonusers (12% reduction; P = 0.115). To minimize impact from ICS withdrawal, in an analysis excluding the first 30 days, FF/UMEC/VI continued to significantly reduce the annual on-treatment moderate/severe exacerbation rate (19%; P < 0.001) compared with UMEC/VI. The benefit of FF/UMEC/VI compared with UMEC/VI was seen for severe exacerbation rates, regardless of prior ICS use (prior ICS users, 35% reduction; P < 0.001; non-ICS users, 35% reduction; P = 0.018), and overall when excluding the first 30 days (29%; P < 0.001). Improvements from baseline with FF/UMEC/VI compared with UMEC/VI were also maintained throughout the study for both trough FEV1 and St. George's Respiratory Questionnaire, regardless of prior ICS use.Conclusions: These data support the important treatment effects of FF/UMEC/VI combination therapy on exacerbation reduction, lung function, and quality of life that do not appear to be related to abrupt ICS withdrawal.Clinical trial registered with www.clinicaltrials.gov (NCT02164513).

• Authors: MeiLan K Han, Gerard J Criner, Mark T Dransfield, David M G Halpin, C Elaine Jones, Sally Kilbride, Peter Lange, Sally Lettis, David A Lipson, David A Lomas, Neil Martin, Robert A Wise, Dave Singh, Fernando J Martinez
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 202 Issue 9 Pg. 1237-1243 (11 01 2020) ISSN: 1535-4970 [Electronic] United States
• PMID: 32584168 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Benzyl Alcohols
• Bronchodilator Agents
• Chlorobenzenes
• GSK573719
• Quinuclidines
• vilanterol
• Fluticasone

Topics

• Administration, Inhalation
• Aged
• Benzyl Alcohols (administration & dosage)
• Bronchodilator Agents (administration & dosage)
• Chlorobenzenes (administration & dosage)
• Double-Blind Method
• Female
• Fluticasone (administration & dosage)
• Humans
• Male
• Middle Aged
• Pulmonary Disease, Chronic Obstructive (drug therapy, physiopathology)
• Quinuclidines (administration & dosage)
• Substance Withdrawal Syndrome (physiopathology)